The role of bio-behavioral factors in the clinical course of the Long QT Syndrome (LQTS) is an understudied phenomenon. The LQTS is a Mendelian-dominant autosomal channelopathy characterized by delayed repolarization, episodic malignant arrhythmias, syncope and sudden death. Substantial progress has been made recently in identifying the genetic and molecular basis for the LQTS. However, there is considerable heterogeneity in the clinical presentation of LQTS that is not well understood. Retrospective studies using relatively insensitive measures suggest that emotions trigger events in all LQTS patients, especially in genotype-2 (LQT2) patients. The proposed research aims to determine whether high intensity negative or positive emotional states increase the likelihood of clinical events in LQTS patients, and whether low intensity negative emotional states increase and low intensity positive emotional states decrease myocardial electrical instability in LQTS patients, especially in LQT2 patients. If the hypothesized associations between emotional states and clinical variables can be established in LQTS, they would have important implications for clinical management of LQTS and would create a foundation for exploring the mechanisms of sudden death in this and other contexts, such as coronary artery disease. The two proposed projects use will state-of-the-art techniques in emotion research that have not previously been used in the context of LQTS. In Study #1, 250 symptomatic LQTS patients will be interviewed by telephone using the case-crossover method for retrospective recall of emotions and other candidate triggers within 1-6 weeks of syncope or aborted cardiac arrest. This study will determine whether emotional triggers occur more frequently prior to clinical events than control time periods. In Study #2, 200 LQTS patients (100 LQT1 and 100 LQT2; each group balanced for gender) will be studied for three consecutive days during which momentary ratings of emotional state will be randomly elicited 7-10 times per day and ambulatory (Holter) ECG monitor recordings will be continuously obtained. During 5-minute epochs corresponding to each set of momentary emotion ratings, Holter recordings will be assessed for indices of myocardial electrical instability, including beat-to-beat changes in repolarization duration, QTc and the high frequency (vagal) component of heart rate variability. The proposed projects capitalize on a well-established NHLBI-funded LQTS registry, a very cooperative patient population, compelling pilot data supporting the proposed hypotheses, an experienced team of investigators and consultants well suited to conduct the proposed study, and outstanding potential for future studies that aim to elucidate the mechanisms linking emotional states and sudden cardiac death.